Product Name:

MLL-pS2196


Product Number:

ab-pn801

Price:

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$98.00
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Target Full Name: Histone-lysine N-methyltransferase MLL

Target Alias: ALL1; ALL-1; CXXC7; HRX; HTRX; HTRX1; KMT2A; MLL1A; Myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); Myeloid/lymphoid or mixed-lineage leukemia (trithorax); Trithorax-like protein; TRX1; Zinc finger protein HRX

Product Type Specific: MLL phosphosite-specific antibody

Antibody Code: PN801

Antibody Target Type: Phosphosite-specific

Antibody Phosphosite: S2196

Protein UniProt: Q03164

Protein SigNET: MLL

Antibody Type: Polyclonal

Antibody Host Species: Rabbit

Antibody Immunogen Source: Synthetic phosphopeptide patterned after human MLL

Antibody Immunogen Sequence: RRH(pS)TSS(βA)C

Antibody Immunogen Description: Corresponds to amino acid residues R2193 to S2199. The effect of S2196 phosphorylation of MLL (KMT2A) is unclear. This is the major in vivo phosphorylation sites in MLL (≥83 reports from high throughput mass spectrometry studies recorded in PhosphoSitePlus).

Production Method: The immunizing peptide was produced by solid phase synthesis on a multipep peptide synthesizer and purified by reverse-phase hplc chromatography. Purity was assessed by analytical hplc and the amino acid sequence confirmed by mass spectrometry analysis. This peptide was coupled to KLH prior to immunization into rabbits. New Zealand White rabbits were subcutaneously injected with KLH-coupled immunizing peptide every 4 weeks for 4 months. The sera from these animals was applied onto an agarose column to which the immunogen peptide was thio-linked. Antibody was eluted from the column with 0.1 M glycine, pH 2.5. Subsequently, the antibody solution was neutralized to pH 7.0 with saturated Tris.

Antibody Modification: Unconjugated. Contact KInexus if you are interest in having the antibody biotinylated or coupled with fluorescent dyes.

Antibody Concentration: 1 mg/ml

Storage Buffer: Phosphate buffered saline pH 7.4, 0.05% Thimerasol

Storage Conditions: For long term storage, keep frozen at -40°C or lower. Stock solution can be kept at +4°C for more than 3 months. Avoid repeated freeze-thaw cycles.

Product Use: Western blotting | Antibody microarray

Antibody Dilution Recommended: 2 µg/ml for immunoblotting

Antibody Species Reactivity: This antibody detects the target phosphoprotein in the following species due to conservation of amino acid sequence: Human | Chimpanzee | Rhesus macaque | Dog | Rat | Mouse.

Scientific Background: MLL (Mixed Lineage Leukemia protein; Lysine Methyltransferase 2A; KMT2A) is a large, 3,969 amino-acid, multi-domain protein (approx. 500 kDa) that belongs to the class V-like SAM-binding methyltransferase superfamily, Histone-lysine methyltransferase family, TRX/MLL subfamily. It plays a critical role in early development and hematopoiesis. It targets histone H3 on lysine 4 (H3K4), facilitating mono-, di-, and tri-methylation (H3K4me1/2/3). This modification is generally associated with active gene transcription. It is essential for early development, since deletion of the MLL gene in mice is embryonic lethal. It is the human homolog of the Drosophila Trithorax (Trx) protein and acts as an epigenetic reader and writer that maintains the expression of homeobox (Hox) genes, which are crucial for body segment identity and hematopoietic stem cell renewal. The protein features several domains including AT-hooks (DNA binding), a CXXC domain (binding unmethylated CpG DNA), plant homeodomains (PHD) for protein-protein interactions, and a C-terminal SET domain. MLL is cleaved by the enzyme Caspase1 into two fragments (N-terminal 320 kDa and C-terminal 180 kDa) that later dimerize to form a functional complex. It binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state. It is required for transcriptional activation of HOXA9. It promotes PPP1R15A-induced apoptosis. It functions in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-BMAL1 heterodimer. It establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-BMAL1 to chromatin. It also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate. MLL cleavage product N320 heterodimerizes with MLL cleavage product C180 (via SET and FYRC domains). It is a component of MLL1/MLL complexes, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, HCFC2, WDR5, DPY30 and RBBP5, as well as the facultative components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. It forms a core complex with the evolutionary conserved subcomplex WRAD composed of WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits; WRAD differentially stimulates the methyltransferase activity. Phosphorylation increases its affinity for PSIP1. It also forms a complex with CREBBP and CREB1. MLL dysfunction typically from chromosomal translocations and fusion products (MLLr), occurs in acute leukemias (both Acute Myeloid Leukemia - AML, and Acute Lymphoblastic Leukemia - ALL), particularly in infants. This description may include information annotated by UniProt and/or Google AI.